Dorsal turning of motor corticospinal axons at the pyramidal decussation requires plexin signaling.
Dorsal turning of motor corticospinal axons at the pyramidal decussation requires plexin signaling.
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DOI：
10.1186/1749-8104-3-21
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发表时间：
2008-08-26
影响因子：
3.6
通讯作者：
Cheng, Hwai-Jong
中科院分区：
文献类型：
--
作者：
Faulkner, Regina L.;Low, Lawrence K.;Liu, Xiao-Bo;Coble, Jeffrey;Jones, Edward G.;Cheng, Hwai-Jong
高等脊椎动物皮质脊髓束（CST）的发育依赖于沿其长投射通路的一系列轴突导向决策沿着。已知几种引导分子参与各种决策点以调节CST轴突的投射。然而，先前对缺乏这些分子的突变小鼠的CST指导缺陷的分析表明，还有其他参与CST轴突指导的分子尚未被确定。在这项研究中，我们调查的作用，丛蛋白信号的指导运动CST轴突在体内。表达模式的研究表明，丛蛋白A3，丛蛋白A4，和neuropilin-1的表达在发育中的大脑皮层时，运动CST轴突起源于层V皮质神经元被引导到脊髓。通过分析突变小鼠，我们表明，运动CST轴突，把背交叉中线在锥体交叉需要丛蛋白A3和丛蛋白A4信号。虽然其他CST的指导缺陷被发现在neuropilin-1突变体，这背转向缺陷没有观察到neuropilin-1或neuropilin-2突变体，这表明激活丛蛋白信号在背转向点的本地线索是膜结合的信号蛋白。进一步的表达模式研究和突变分析表明，Sema 6A是运动CST轴突转向在锥体交叉的局部线索之一。在锥体交叉处的背侧转向和中线交叉是正确引导CST轴突进入背侧脊髓的关键步骤。我们发现，plexin-A3，plexin-A4，和Sema 6A的信号至少部分需要背侧转向的CST轴突，而neuropilin-1需要适当的束在中线交叉。与以前的报告一起，这些结果表明，几个指导线索是专门用来调节背转向和中线交叉的发展中CST轴突。
The development of the corticospinal tract (CST) in higher vertebrates relies on a series of axon guidance decisions along its long projection pathway. Several guidance molecules are known to be involved at various decision points to regulate the projection of CST axons. However, previous analyses of the CST guidance defects in mutant mice lacking these molecules have suggested that there are other molecules involved in CST axon guidance that are yet to be identified. In this study, we investigate the role of plexin signaling in the guidance of motor CST axons in vivo. Expression pattern studies show that plexin-A3, plexin-A4, and neuropilin-1 are expressed in the developing cerebral cortex when the motor CST axons originating from layer V cortical neurons are guided down to the spinal cord. By analyzing mutant mice, we show that motor CST axons that turn dorsally to cross the midline at the pyramidal decussation require plexin-A3 and plexin-A4 signaling. Although other CST guidance defects are found in neuropilin-1 mutants, this dorsal turning defect is not observed in either neuropilin-1 or neuropilin-2 mutants, suggesting that the local cues that activate plexin signaling at the dorsal turning point are membrane-bound semaphorins. Further expression pattern study and mutant analysis indicate that Sema6A is one of the local cues for motor CST axon turning at the pyramidal decussation. Dorsal turning and midline crossing at the pyramidal decussation is a crucial step to properly direct CST axons into the dorsal spinal cord. We show that the signaling of plexin-A3, plexin-A4, and Sema6A is at least partially required for dorsal turning of the CST axons, while neuropilin-1 is required for proper fasciculation of the tract at midline crossing. Together with previous reports, these results demonstrate that several guidance cues are specifically utilized to regulate the dorsal turning and midline crossing of developing CST axons.
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影响因子：
16.2
作者：
Chen, H;Bagri, A;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
11.4
作者：
Castellani, V;De Angelis, E;Rougon, G
通讯作者：
Rougon, G
影响因子：
16.2
作者：
Castellani, V;Chédotal, A;Rougon, G
通讯作者：
Rougon, G
影响因子：
11.8
作者：
Gu, CH;Rodriguez, ER;Ginty, DD
通讯作者：
Ginty, DD
影响因子：
16.2
作者：
Arlotta, P;Molyneaux, BJ;Macklis, JD
通讯作者：
Macklis, JD